Over 30% of patients infected with HIV develop thrombocytopenia over the course of their illness. Current models of thrombocytopenia are based upon those of immune thrombocytopenia purpura (ITP). However ITP is characterized by immunologic destruction of platelets, with notably shortened platelet half-life, which is not characteristic of many patients with severe, unexplained HIV-associated thrombocytopenia. The proposed research investigates an HIV-mediated defect in SDF1 directed megakarocyte migration through bone marrow stroma. This is hypothesized to be a mechanism for HIV-associated thrombocytopenia. The specific aims are to 1) Elucidate the mechanism of inhibition of migration in HIV infected megakaryocytes and 2) Explore whether the in vitro inhibition of migration observed is likely the in vivo cause of HIV associated thrombocytopenia. Methods used will include: pharmacologic and molecular techniques to target proteins in the SDF1 signal transduction pathway, analysis of dominant negative mutations, immunoblotting, competitive inhibition studies, ELISA assays, RT-PCR and flow cytometry. Further elucidation of this pathway may facilitate the development of novel strategies to treat HIV thrombocytopenia.